In response to the National Cancer Institute re-issue of the Transdisciplinary Research on Energetics and Cancer (TREC) initiative (RFA-CA-10-006), we propose to establish a TREC Center that draws on the multidisciplinary expertise of the faculty of Harvard University at the Harvard School of Public Health (HSPH), Harvard Medical School and the Harvard-affiliated Brigham and Women's Hospital, Boston Children's Hospital, Dana-Farber/Harvard Cancer Center, Harvard Pilgrim Health Care Institute, and the Harvard Center for Population and Development Studies. We have developed four complementary and interrelated research projects which are supported by four cores and additional existing resources at the participating institutions. Together, they form a cohesive, transdisciplinary center focused on the generation of new knowledge and its translation, training, and career development. In Project 1, we will examine sleep duration, energy balance, and insulin resistance among children in Project Viva; in Project 2, we will examine the relation of energetic factors (including dietary insulin demand, objectively measured energy expenditure, and physical activity), sleep duration, and the built environment with novel cancer biomarkers (insulin-IGF axis, adipokines, and sex hormones) in the Nurses' Health Study; in Project 3, we will examine the relation of energetic factors (dietary insulin demand, adiposity, and physical activity) and biomarkers of the insulin/IGF pathway with prostate cancer survivorship in the Physicians' Health Study; and in Project 4, we will conduct a randomized trial to evaluate whether a theory-based exercise intervention, alone or in combination with a pharmacological intervention, decreases circulating levels of insulin and other biomarkers previously linked to poor prognosis among colorectal cancer survivors. These projects will be supported by four cores: Administrative, Education/Training, Bioinformatics, and Developmental. Through these highly integrated projects and supporting Cores, we aim to train postdoctoral fellows and junior faculty in a transdisciplinary environment to pursue careers in energetics and cancer and to foster innovative transdisciplinary research projects that build on the Center's and the overall TREC program's vision and resources. We have obtained strong institutional commitment, as outlined in the letters from Dr. Julio Frenk, Dean of the Faculty, Harvard School of Public Health, and Dr. Edward Benz, Director of the DF/HCC and President of the Dana-Farber Cancer Institute. By leveraging multiple areas of expertise and different resources within and across TREC centers, we can help further build a unique national resource of energetics and cancer knowledge.